Clinical and Immunological Features of Human BCL10 Deficiency

The CARD-BCL10-MALT1 (CBM) complex is critical for the proper assembly of human immune responses. The clinical and immunological consequences of deficiencies in some of its components such as CARD9, CARD11, and MALT1 have been elucidated in detail. However, the scarcity of BCL10 deficient patients h...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Blanca Garcia-Solis, Ana Van Den Rym, Jareb J. Pérez-Caraballo, Abdulwahab Al–Ayoubi, Anas M. Alazami, Lazaro Lorenzo, Carolina Cubillos-Zapata, Eduardo López-Collazo, Antonio Pérez-Martínez, Luis M. Allende, Janet Markle, Miguel Fernández-Arquero, Silvia Sánchez-Ramón, Maria J. Recio, Jean-Laurent Casanova, Reem Mohammed, Rubén Martinez-Barricarte, Rebeca Pérez de Diego
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	primary immunodeficiency combined immunodeficiency BCL10 autosomal recessive mass cytometry computational immunology Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/8741b9bb80a4423bab400712dd1659fa
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8741b9bb80a4423bab400712dd1659fa
record_format	dspace
spelling	oai:doaj.org-article:8741b9bb80a4423bab400712dd1659fa2021-11-12T07:11:34ZClinical and Immunological Features of Human BCL10 Deficiency1664-322410.3389/fimmu.2021.786572https://doaj.org/article/8741b9bb80a4423bab400712dd1659fa2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.786572/fullhttps://doaj.org/toc/1664-3224The CARD-BCL10-MALT1 (CBM) complex is critical for the proper assembly of human immune responses. The clinical and immunological consequences of deficiencies in some of its components such as CARD9, CARD11, and MALT1 have been elucidated in detail. However, the scarcity of BCL10 deficient patients has prevented gaining detailed knowledge about this genetic disease. Only two patients with BCL10 deficiency have been reported to date. Here we provide an in-depth description of an additional patient with autosomal recessive complete BCL10 deficiency caused by a nonsense mutation that leads to a loss of expression (K63X). Using mass cytometry coupled with unsupervised clustering and machine learning computational methods, we obtained a thorough characterization of the consequences of BCL10 deficiency in different populations of leukocytes. We showed that in addition to the near absence of memory B and T cells previously reported, this patient displays a reduction in NK, γδT, Tregs, and TFH cells. The patient had recurrent respiratory infections since early childhood, and showed a family history of lethal severe infectious diseases. Fortunately, hematopoietic stem-cell transplantation (HSCT) cured her. Overall, this report highlights the importance of early genetic diagnosis for the management of BCL10 deficient patients and HSCT as the recommended treatment to cure this disease.Blanca Garcia-SolisBlanca Garcia-SolisBlanca Garcia-SolisAna Van Den RymAna Van Den RymAna Van Den RymJareb J. Pérez-CaraballoJareb J. Pérez-CaraballoAbdulwahab Al–AyoubiAnas M. AlazamiLazaro LorenzoCarolina Cubillos-ZapataCarolina Cubillos-ZapataEduardo López-CollazoAntonio Pérez-MartínezAntonio Pérez-MartínezLuis M. AllendeJanet MarkleJanet MarkleMiguel Fernández-ArqueroMiguel Fernández-ArqueroSilvia Sánchez-RamónSilvia Sánchez-RamónMaria J. RecioMaria J. RecioJean-Laurent CasanovaJean-Laurent CasanovaJean-Laurent CasanovaJean-Laurent CasanovaReem MohammedReem MohammedRubén Martinez-BarricarteRubén Martinez-BarricarteRebeca Pérez de DiegoRebeca Pérez de DiegoRebeca Pérez de DiegoFrontiers Media S.A.articleprimary immunodeficiencycombined immunodeficiencyBCL10autosomal recessivemass cytometrycomputational immunologyImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	primary immunodeficiency combined immunodeficiency BCL10 autosomal recessive mass cytometry computational immunology Immunologic diseases. Allergy RC581-607
spellingShingle	primary immunodeficiency combined immunodeficiency BCL10 autosomal recessive mass cytometry computational immunology Immunologic diseases. Allergy RC581-607 Blanca Garcia-Solis Blanca Garcia-Solis Blanca Garcia-Solis Ana Van Den Rym Ana Van Den Rym Ana Van Den Rym Jareb J. Pérez-Caraballo Jareb J. Pérez-Caraballo Abdulwahab Al–Ayoubi Anas M. Alazami Lazaro Lorenzo Carolina Cubillos-Zapata Carolina Cubillos-Zapata Eduardo López-Collazo Antonio Pérez-Martínez Antonio Pérez-Martínez Luis M. Allende Janet Markle Janet Markle Miguel Fernández-Arquero Miguel Fernández-Arquero Silvia Sánchez-Ramón Silvia Sánchez-Ramón Maria J. Recio Maria J. Recio Jean-Laurent Casanova Jean-Laurent Casanova Jean-Laurent Casanova Jean-Laurent Casanova Reem Mohammed Reem Mohammed Rubén Martinez-Barricarte Rubén Martinez-Barricarte Rebeca Pérez de Diego Rebeca Pérez de Diego Rebeca Pérez de Diego Clinical and Immunological Features of Human BCL10 Deficiency
description	The CARD-BCL10-MALT1 (CBM) complex is critical for the proper assembly of human immune responses. The clinical and immunological consequences of deficiencies in some of its components such as CARD9, CARD11, and MALT1 have been elucidated in detail. However, the scarcity of BCL10 deficient patients has prevented gaining detailed knowledge about this genetic disease. Only two patients with BCL10 deficiency have been reported to date. Here we provide an in-depth description of an additional patient with autosomal recessive complete BCL10 deficiency caused by a nonsense mutation that leads to a loss of expression (K63X). Using mass cytometry coupled with unsupervised clustering and machine learning computational methods, we obtained a thorough characterization of the consequences of BCL10 deficiency in different populations of leukocytes. We showed that in addition to the near absence of memory B and T cells previously reported, this patient displays a reduction in NK, γδT, Tregs, and TFH cells. The patient had recurrent respiratory infections since early childhood, and showed a family history of lethal severe infectious diseases. Fortunately, hematopoietic stem-cell transplantation (HSCT) cured her. Overall, this report highlights the importance of early genetic diagnosis for the management of BCL10 deficient patients and HSCT as the recommended treatment to cure this disease.
format	article
author	Blanca Garcia-Solis Blanca Garcia-Solis Blanca Garcia-Solis Ana Van Den Rym Ana Van Den Rym Ana Van Den Rym Jareb J. Pérez-Caraballo Jareb J. Pérez-Caraballo Abdulwahab Al–Ayoubi Anas M. Alazami Lazaro Lorenzo Carolina Cubillos-Zapata Carolina Cubillos-Zapata Eduardo López-Collazo Antonio Pérez-Martínez Antonio Pérez-Martínez Luis M. Allende Janet Markle Janet Markle Miguel Fernández-Arquero Miguel Fernández-Arquero Silvia Sánchez-Ramón Silvia Sánchez-Ramón Maria J. Recio Maria J. Recio Jean-Laurent Casanova Jean-Laurent Casanova Jean-Laurent Casanova Jean-Laurent Casanova Reem Mohammed Reem Mohammed Rubén Martinez-Barricarte Rubén Martinez-Barricarte Rebeca Pérez de Diego Rebeca Pérez de Diego Rebeca Pérez de Diego
author_facet	Blanca Garcia-Solis Blanca Garcia-Solis Blanca Garcia-Solis Ana Van Den Rym Ana Van Den Rym Ana Van Den Rym Jareb J. Pérez-Caraballo Jareb J. Pérez-Caraballo Abdulwahab Al–Ayoubi Anas M. Alazami Lazaro Lorenzo Carolina Cubillos-Zapata Carolina Cubillos-Zapata Eduardo López-Collazo Antonio Pérez-Martínez Antonio Pérez-Martínez Luis M. Allende Janet Markle Janet Markle Miguel Fernández-Arquero Miguel Fernández-Arquero Silvia Sánchez-Ramón Silvia Sánchez-Ramón Maria J. Recio Maria J. Recio Jean-Laurent Casanova Jean-Laurent Casanova Jean-Laurent Casanova Jean-Laurent Casanova Reem Mohammed Reem Mohammed Rubén Martinez-Barricarte Rubén Martinez-Barricarte Rebeca Pérez de Diego Rebeca Pérez de Diego Rebeca Pérez de Diego
author_sort	Blanca Garcia-Solis
title	Clinical and Immunological Features of Human BCL10 Deficiency
title_short	Clinical and Immunological Features of Human BCL10 Deficiency
title_full	Clinical and Immunological Features of Human BCL10 Deficiency
title_fullStr	Clinical and Immunological Features of Human BCL10 Deficiency
title_full_unstemmed	Clinical and Immunological Features of Human BCL10 Deficiency
title_sort	clinical and immunological features of human bcl10 deficiency
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/8741b9bb80a4423bab400712dd1659fa
work_keys_str_mv	AT blancagarciasolis clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT blancagarciasolis clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT blancagarciasolis clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT anavandenrym clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT anavandenrym clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT anavandenrym clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT jarebjperezcaraballo clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT jarebjperezcaraballo clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT abdulwahabalayoubi clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT anasmalazami clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT lazarolorenzo clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT carolinacubilloszapata clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT carolinacubilloszapata clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT eduardolopezcollazo clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT antonioperezmartinez clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT antonioperezmartinez clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT luismallende clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT janetmarkle clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT janetmarkle clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT miguelfernandezarquero clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT miguelfernandezarquero clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT silviasanchezramon clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT silviasanchezramon clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT mariajrecio clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT mariajrecio clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT jeanlaurentcasanova clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT jeanlaurentcasanova clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT jeanlaurentcasanova clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT jeanlaurentcasanova clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT reemmohammed clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT reemmohammed clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT rubenmartinezbarricarte clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT rubenmartinezbarricarte clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT rebecaperezdediego clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT rebecaperezdediego clinicalandimmunologicalfeaturesofhumanbcl10deficiency AT rebecaperezdediego clinicalandimmunologicalfeaturesofhumanbcl10deficiency
_version_	1718431118729936896

Clinical and Immunological Features of Human BCL10 Deficiency

Ejemplares similares